Study the effects of 17β-estrodiol on CCl_4-induced liver fibrosis in rats

Objective To investigate the effects of 17β-estrodiol (E_2) on capillarization of CCl_4-induced rat liver fibrosis.Methods Eighty Wistar rats (40M,40F), weight (200±17) g were divided into thres group. For CCl_4 group (n=30), 60% CCl_4 in peanut oil was injected subcutaneously at a dose of 2 ml/kg twice weekly, and the first dosage was doubled. The E_2 group(n=30), in addition to CCl_4, rats were injected subcutaneausly with E_2 200 μg/kg once weekly. Twenty rats were served as control 4-6 rats were fasted overnight and sacrified every 3 weeks. The serum obtained was analysed for liver function tested. Liver tissues from each rat were stained with hematoxylin-eosin (H-E) and masson’s trichrome. Expression of NF-kB P65 mRNA were detected by immunohistochemistry, hybrization in situ and TEM were performed. Results The results revealed that CCl_4 produced a marked increase in the activities of serum ALT, AST, hepatic fibrosis stage in both male and female rats. After administration of 17β-estradiol, the enzyme levels and the stage of hepatic fibrosis were significantly decreased than that of CCl_4 only groups (P0.05,P0.01). Analysis of NF-κB P65 mRNA expression by hybridization in situ showed that positive staining cells was (21.70±5.93)% and (46.19±6.73)% at the 6 th and 12 th week in CCl_4 group respectively. They were higher significantly compared with that in E_2 group (15.36±4.41)%, (31.51±6.02)% (P0.05,P0.01). Transmission electron microscopy showed that the hepatocellular damage of CCl_4 group rats was more serious than E_2 group, with much deposition of extracellular matrix and collagen fibers.Conclusion E_2 could downregulate the expression of NF-κB P65 mRNA in rat liver tissues and block the signal transconduct that led to liver fibrosis. E_2 could improve liver function and reduce the damages of hepatocytes induced by CCl_4, it may play an important role as an endogenous fibrosuppressant in fibrosis, accounting for sex-associated differences in the progression from hepatic fibrosis to cirrhosis.